The Search for Criteria to Assess the Risks Resulting from Exposure to Carcinogenic Agents

  • Umberto Saffiotti


The increasingly rapid developments of toxicological research in the last few decades confronted us with the problem of correlating new scientific knowledge with its public health implications. Progressively more attention has been given to the nature of “selfreplicating toxic effects,” such as mutagenicity and carcinogenicity, in comparison with the “terminal toxic effects” studied by traditional toxicology [1]. Self-replicating toxic effects usually have the following characteristics: a) their appearance is delayed, often by a period of time as long as one-half or more of the lifetime of the host; b) the frequency of the expression of injury (e.g., tumor incidence) in the exposed population is directly correlated with the intensity of the exposure, but the intensity of the induced pathology (e.g., tumor growth and spread) is independent of the intensity of the exposure to the toxic agent; and c) the manifestations of toxicity are due to the proliferative response of a new altered cell population. Terminal toxic effects, on the other hand, usually have these different characteristics: a) they appear early after exposure to the toxic agents, b) the intensity of the induced pathology is directly correlated with the intensity of the toxic exposure, and c) the manifestations of toxicity are due either to altered functional products of the target tissues or to degenerative changes or death of the target cells themselves.


Carcinogenic Risk Public Health Implication Total Cancer Incidence Animal Bioassay Carcinogenic Hazard 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    U. Saffiotti, Scientific bases of environmental carcinogenesis and cancer prevention: developing an interdisciplinary science and facing its ethical implications, J. Toxicol. Environ. Health 2:1435 (1977).Google Scholar
  2. 2.
    International Union Against Cancer, Report of Symposium on potential cancer hazards from chemical additives and contaminants to foodstuffs, Acta Unio Intl. Contra Cancrum 13:170 (1957).Google Scholar
  3. 3.
    P. Shubik and J. Sice, Chemical carcinogenesis as a chronic toxicity test. A review, Cancer Res. 16: 728 (1956).Google Scholar
  4. 4.
    Food Protection Committee, Food and Nutrition Board, Problems in the evaluation of carcinogenic hazards from the use of food additives, Cancer Res. 21: 429 (1961).Google Scholar
  5. 5.
    Fifth Report of the Joint FAO/WHO Expert Committee on Food Additives, Evaluation of carcinogenic hazards of food additives, WHO Tech. Rept. Series 220 (1961).Google Scholar
  6. 6.
    I. Berenblum, ed., Carcinogenicity Testing, UICC Tech. Rept. Series (1969).Google Scholar
  7. 7.
    J. M. Sontag, N. P. Page, and U. Saffiotti, Guidelines for carcinogen bioassay in small rodents, NCI Tech. Rept. Series No. 1, DHEW Publ. No. (NIH)76–801 (1976).Google Scholar
  8. 8.
    Health and Welfare, Canada, The testing of chemicals for carcinogenicity, mutagenicity, and teratogenicity, Health and Welfare, Ottawa, Canada (1973).Google Scholar
  9. 9.
    International Agency for Research on Cancer, Long-term and short-term screening assays for carcinogens: A critical appraisal, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans Supp. 2, IARC, Lyon (1980).Google Scholar
  10. 10.
    Interagency Regulatory Liaison Group, Work Group on Assessment, Scientific bases for identification of potential carcinogens and estimation of risks, J. Natl. Cancer Inst. 63:241 (1979).Google Scholar
  11. 11.
    U. Saffiotti, Identification and definition of chemical carcinogens: Review of criteria and research needs. J. Toxicol. Environ. Health 6:1029 (1980).Google Scholar
  12. 12.
    U. Saffiotti, The problem of extrapolating from observed carcinogenetic effects to estimates of risk for exposed populations. J. Toxicol. Environ. Health 6:1309 (1980).Google Scholar
  13. 13.
    R. A. Griesemer and C. Cueto, Jr., Toward a classification scheme for degrees of experimental evidence for the carcinogenicity of chemicals for animals, in: “Molecular and Cellular Aspects of Carcinogen Screening Tests,” R. Montesano, H. Bartsch, and L. Tomatis, eds., IARC, Lyon (1980).Google Scholar
  14. 14.
    U. Saffiotti and N. P. Page, Releasing carcinogenesis test results: Timing and extent of reporting, Med. Pediatr. Oncol. 3:159 (1977).Google Scholar
  15. 15.
    R. Montesano, H. Bartsch, and L. Tomatis, Screening tests in chemical carcinogenesis, IARC Scientific Publ. No. 12, International Agency for Research on Cancer, Lyon (1976).Google Scholar
  16. 16.
    U. Saffiotti and H. Autrup, In vitro carcinogenesis. Guide to the literature, recent advances and laboratory procedures. NCI Carcinogenesis Tech. Rept. Series No. 44, DHEW Publ. (NIH)78–844 (1978).Google Scholar
  17. 17.
    Methods for carcinogenesis tests at the cellular level and their evaluation for the assessment of occupational cancer hazards.“ Proceedings of the Meeting of the Scientific Committee, Fondazione Carlo Erba, Milan (1977).Google Scholar
  18. 18.
    U. Saffiotti, The multifactorial origin of cancer: A proposed model for studies on the interaction of multiple concurring factors (submitted for publication).Google Scholar
  19. 19.
    U. Saffiotti, Occupational carcinogens in relation to the multifactorial origin of cancer: Experimental pathology approaches, Proc. Internat. Symposium on Prevention of Occupational Cancer, Helsinki, ILO, Geneva (1981) (in press).Google Scholar
  20. 20.
    D. G. Hoel, D. W. Gaylor, R. L.Kirschstein, U. Saffiotti, and M. A. Schneiderman, Estimation of risks of irreversible, delayed toxicity, J. Toxicol. Environ. Health 1:133 (1975).Google Scholar
  21. 21.
    U. Saffiotti, Experimental identification of chemical carcinogens, risk evaluation and animal-to-human correlations, Environ. Health Perspect. 22:107 (1978).Google Scholar
  22. 22.
    M. W. Anderson, D. G. Hoel, and N. L. Kaplan, A general scheme for the incorporation of pharmacokinetics in low-dose risk estimation for chemical carcinogenesis: Example - vinyl chloride, Toxicol. Appl. Pharmacol. 55:154 (1980).Google Scholar
  23. 23.
    T. C. Campbell, Chemical carcinogens and human risk assessment, Fed. Proc. 39:2467 (1980).Google Scholar
  24. 24.
    Committee on Prototype Explicit Analyses for Pesticides, National Research Council, “Regulating pesticides,” National Academy of Sciences, Washington, D.C. (1980).Google Scholar
  25. 25.
    W. J. Nicholson, ed., “Management of Assessed Risk for Carcinogens,” Ann. New York Acad. Sci., Vol. 363, New York (1981).Google Scholar
  26. 26.
    M. Meselson and K. Russell, Comparison of carcinogenic and mutagenic potency, in: “Origins of Human Cancer,” H. H. Hiatt, J. D. Watson, and J. A. Winsten, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York (1977).Google Scholar
  27. 27.
    Environmental Studies Board, National Research Council, Carcinogenesis in man and laboratory animals, in: Pest Control: An Assessment of Present and Alternative Technologies. Vol. 1. Contemporary Pest Control Practices and Prospects, National Academy of Sciences, Washington, D.C. (1975).Google Scholar
  28. 28.
    E. L. Wynder and G. B. Gori, Contribution of the environment to cancer incidence: An epidemiologic exercise, J. Natl. Cancer Inst. 58:825 (1977).Google Scholar
  29. 29.
    J. Higginson and C. S. Muir, Environmental carcinogenesis: Misconceptions and limitations to cancer control, J. Natl. Cancer Inst. 63:1291 (1979).Google Scholar
  30. 30.
    K. Bridbord, P. Decoufle, J. F. Fraumeni, D. G. Hoel, R. N. Hoover, D. P. Rall, U. Saffiotti, M. A. Schneiderman, and A. C. Upton (contributors), National Cancer Institute, National Institute of Environmental Health Sciences and National Institute for Occupational Safety and Health, Estimates of the fraction of cancer in the United States related to occupational factors, Testimony submitted on September 15, 1978, to the U.S. Occupational Safety and Health Administration on proposed regulations for the identification, classification and regulation of toxic substances posing a potential occupational carcinogenic risk to humans, OSHA, Washington, D.C. (1978).Google Scholar
  31. 31.
    J. Higginson, Multiplicity of factors involved in cancer patterns and trends, J. Environ. Pathol. Toxicol. 3:113 (1980).Google Scholar
  32. 32.
    R. Doll and R. Peto, The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today, J. Natl. Cancer Inst. 66:1191 (1981).Google Scholar
  33. 33.
    U. Saffiotti and C. C. Harris, Carcinogenesis studies on organ cultures of animal and human respiratory tissues, in: Carcinogens: Identification and Mechanisms of Action, A. C. Griffin and C. R. Shaw, Raven, New York (1979).Google Scholar
  34. 34.
    L. M. Franks and C. B. Wigley, “Neoplastic Transformation in Differentiated Epithelial Cell Systems in vitro,” Academic Press, London (1979).Google Scholar
  35. 35.
    C. C. Harris, B. F. Trump, and G. D. Stoner, “Methods in Cell Biology,” Vol. 21, Normal Human Tissue and Cell Culture, Academic Press, New York (1980).Google Scholar

Copyright information

© Springer Science+Business Media New York 1983

Authors and Affiliations

  • Umberto Saffiotti
    • 1
  1. 1.Laboratory of Experimental Pathology Division of Cancer Cause and PreventionNational Cancer InstituteFrederickUSA

Personalised recommendations